Drug combinations with quercetin: doxorubicin plus quercetin in human breast cancer cells
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Doxorubicin is a first-line chemotherapeutic for breast cancer; however, it is associated with severe side effects to non-tumoral tissues. Thus, it is necessary to develop new therapeutic combinations to improve doxorubicin effects at lower concentration of the drug associated with protective effects for non-tumoral cells. In this work, we evaluated whether the plant-derived flavonoid quercetin may represent such an agent.
The effects of doxorubicin and quercetin as single agents and in combination were evaluated on cell survival, DNA and protein synthesis, oxidative stress, migratory potential and cytoskeleton and nucleus structure in highly invasive and poorly invasive human breast cancer cells in comparison with non-tumoral human breast cells.
In human breast cancer cells, quercetin potentiated antitumor effects of doxorubicin specifically in the highly invasive breast cancer cells and attenuated unwanted cytotoxicity to non-tumoral cells. Quercetin interfered with cell metabolism, GST activity, cytoskeleton and invasive properties specifically in breast tumor cells compared with non-tumoral breast cells. Doxorubicin induced DNA damage in tumor and non-tumor cells; however, quercetin reduced this damage only in non-tumoral cells, thus offering a protective effect for these cells. Quercetin also induced polynucleation in aggressive tumor cells, which was maintained in combination with doxorubicin.
By combining quercetin with doxorubicin, an increase in doxorubicin effects was obtained specifically in the highly invasive breast cancer cells, while in non-tumoral cells quercetin reduced doxorubicin cytotoxic side effects. Thus, quercetin associated with doxorubicin demonstrated very promising properties for developing chemotherapeutics combinations for the therapy of breast cancer.
KeywordsQuercetin Doxorubicin Breast cancer cells Tyrosine protein kinases Polynucleation Genotoxicity
We want to thank Dr. C. Brisken for the kind gift of MCF-10A cells, Dr. F. Schmitt for very helpful discussions and comments, Ms. C. Chapuis Bernasconi for excellent technical assistance, and the European Community FP7 project “NanoTest” (grant No 2007-201335) for financial support (to BHK and LJJ). The results shown here are part of Master thesis work of E. Idrizi and D. Staedler at the University of Lausanne (UNIL).
Conflict of interest
The authors declare no conflict of interest.
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